tbuckley/cabot-search huggingface dataset:
Abstract 13869: The Association Between <i>DYRK4</i> Hypomethylation in Peripheral Blood and Coronary Heart Disease: A Case-Control Study
Authors: Rongxi Yang, jialie jin, yakang song, ruotian zhang, yining yang
Journal: Circulation (2023)

Backgrounds: Coronary heart disease (CHD) is a leading cause of morbidity and mortality worldwide, with myocardial infarction (MI) representing its most prevalent type. Previous studies have suggested an association between the dual-specificity tyrosine-regulated kinases ( DYRK) gene family and various cardiovascular disease risks. However, the specific role of DYRK4 in CHD, particularly in MI, remains unclear. Objective: We hereby investigated the association between blood-based DYRK4 methylation and CHD, MI and non-MI related CHD. Methods: A total of 88 CHD cases (23 MI and 65 non-MI) were diagnosed by coronary angiography and clinical presentation at Chinese People's Liberation Army General Hospital from 2018 to 2019. 93 persons who participated in the annual health examination were randomly selected as controls. The DYRK4 methylation, which contains three measurable CpG sites, was quantified by mass spectrometry of nucleic acid. Covariates-adjusted odds ratios (ORs) for -10% methylation was calculated by binary logistic regression, and receiver operating characteristic (ROC) curves were generated to evaluate the discriminatory power. Results: Decreased methylation of DYRK4_CpG_2 and DYRK4_CpG_3 in peripheral blood was significantly associated with increased CHD risk (OR: 1.49 and 1.20; p = 0.044 and 0.049). Notably, these two CpG sites were only significant in non-MI related CHD (OR: 1.71 and 1.33; p = 0.015 and 0.009) rather than MI (OR: 1.11 and 0.99; p = 0.759 and 0.968). The combination of DYRK4_CpG_2 and DYRK4_CpG_3 methylation levels could efficiently discriminate CHD, MI and non-MI related CHD patients from controls (area under curve (AUC) = 0.771, 0.795 and 0.784, respectively). Conclusion: Our study suggests that hypomethylation of DYRK4_CpG_2, DYRK4_CpG_3 in blood is associated with CHD, and DYRK4 methylation model may provide a new strategy for detection of CHD, especially non-MI related CHD.
Abstract 13892: Enhancing Guideline-Directed Medical Therapy in Post-Discharge Heart Failure Patients Through Comprehensive Medication Management Visits With Virtual Clinical Pharmacists
Authors: Melanie Plotke, Tram Thai, Farrukh Jafri
Journal: Circulation (2023)

Introduction: According to national registries, the adoption and effective titration of GDMT for patients with HFrEF remains notably inadequate. Utilizing virtual clinical pharmacists (VCPs) to identify deficiencies in medication therapy presents a flexible and efficient approach for thorough and immediate interventions following discharge. Methods: A single-center retrospective analysis from May 2022-April 2023 examined post-discharge HF patients who participated in a comprehensive medication management (CMM) visit conducted by a VCP within 72 hours of their discharge. Results: Of 116 participants, 108 (93%) had a discharge diagnosis of HFrEF, and 8 (6.8%) with HFimpEF. During the VCP visit, 27 (23.3%) presented with active HF exacerbation symptoms including SOB (33%), fatigue (22%), weakness (19%), lower extremity swelling (11%), weight gain (11%), and tachycardia (4%). The percentages of the total population currently prescribed GDMT for HRrEF and HFimpEF classes are as follows: Beta Blocker (89.7%), ARNI (47.4%), MRA (33.6%), SGLT2i (25.9%), and ACEI/ARB (22.4%). Up-titrating of dosage was recommended for 75% of patients currently prescribed ARNI, 64% for Beta Blockers, and 51% for MRAs. Additionally, VCPs recommended adding the following drug classes to those not prescribed, despite being indicated: SGLT2i (45%), ARNI (30%), MRA (29%), Beta Blocker (25%), and ACEI/ARB (24%). Comprehensive counseling on HF self-care practices was delivered to the entire cohort (100%). Furthermore, support was extended to facilitate the management of comorbid conditions for 105 patients (91%), and social assistance was provided to 7 patients (6%). Conclusions: The utilization of VCPs played a crucial role in identifying care gaps, including but not limited to patient symptoms, suboptimal medication therapy, insufficient disease education, social assistance, and comorbidity management, which collectively contributed to initiating and up-titrating GDMT.
Abstract 12573: Differences in Blood Product Consumption Between Ventricular Assist Device and Extracorporeal Membrane Oxygenation During Postoperative Period
Authors: Juthipong Benjanuwattra, Rachel Liao, Nandini Nair
Journal: Circulation (2023)

Introduction: Mechanical circulatory supports such as veno-arterial extracorporeal membrane oxygenation (ECMO) and left ventricular assist device (LVAD) are used in advanced heart failure patients. Due to their thrombogenic surfaces, these devices can lead to disseminated thrombosis. The need for anticoagulation also predisposes to hemorrhage, in addition to hemolysis from shear stress. As a result, transfusion of blood components is usually warranted following implantation. Hypothesis: To evaluate the differences in the need for transfusion of blood products between these devices during immediate postoperative period up to day 3. Methods: Fifty-four patients with advanced heart failure patients admitted at our facility between January 2016-2019 were included. All patients were anticoagulated with continuous heparin infusion. We analyzed the need for packed red blood cells (pRBC), fresh frozen plasma (FFP), and platelet transfusion. Lactate dehydrogenase (LDH), CBC, aPTT, and PT were also measured. The study was approved by Institutional Review Board (#L19-093). Results: A total of 54 patients (25 patients received ECMO and 29 patients received LVAD) were included. The median age was 56 years [47-62]. Thirty-eight patients (70.4%) were male. The means daily substitution of pRBC were significantly lower in the LVAD group on day 2 (0.35 vs 2.64 units/day, p=0.002) and day 3 (0.58 vs 1.64 units/day, p=0.028). The means daily substitution of platelets were comparable between the ECMO and LVAD groups. A trend toward the lower mean daily substitution of FFP in the LVAD group on day 2 (0 vs 0.44 units/day, p=0.069) was seen. There was a significantly lower serum LDH in the LVAD group on day 3 (391 ± 345 vs 599 ± 268, p=0.003). Conclusions: Data from this retrospective study showed that, compared to ECMO, LVAD was associated with lower rates of hemolysis and pRBC transfusion.
Abstract 16927: The Mother of All Pseudoaneurysms - A Rare Case
Authors: Anjula Chib, Vivek Menon, Michael Ghaly, Anan Abu Rmilah, Sasha Sharifi, Talhah Siraj, Sophia Thang, MANDAR JAGTAP DO, Nanni Pidikiti, Mehul Patel, AMY PARKER, Paul Volansky
Journal: Circulation (2023)

Introduction: Femoral artery pseudoaneurysms (FAP) are typically caused by percutaneous access during coronary and peripheral angiography. It occurs in 0.1 to 0.2% of diagnostic catheterization procedures and in 3.5% to 5.5% of interventional procedures. Cases of “Giant” femoral artery pseudoaneurysms have seldom documented in the past, however, our case is unique for two reasons:- Pseudoaneurysm presented 6 months after femoral arterial access, which is unusual.- This size of pseudo-aneurysm has yet to be documented. Case Description: 74-year-old male with history of diabetes mellitus type II and tobacco abuse presented with chest pain. He underwent cardiac catheterization via radial access, which confirmed severe multi-vessel disease with ejection fraction of 30%. Patient was started on goal-directed medical therapy with planned elective IABP-assisted coronary artery bypass grafting (CABG). On the day of surgery in anticipation of IABP, right femoral artery was accessed, however, intra-operative transesophageal echocardiography showed improvement of ejection fraction to 55%, which led to removal of the femoral sheath and application of a closure device. Six months later, patient presented with a large right groin mass. Computed tomography angiography confirmed a pseudoaneurysm anterior to the right common femoral artery, measuring 9.6 cm x 9.8 cm causing moderate stenosis of the superficial femoral artery. Peripheral arterial duplex ascertained the neck of pseudoaneurysm measuring 1.3 cm. Patient underwent emergent repair of the right femoral pseudoaneurysm, with thrombus removal. No further recurrence of pseudoaneurysm was noted. Discussion: Pseudoaneurysms may arise months after femoral arterial access. Any groin symptoms in patients who underwent percutaneous femoral arterial access warrant additional investigation. Further studies are needed to elucidate the factors that increase the risk of formation and rupture of pseudoaneurysms
Abstract 13871: Portrayal of Acute Myocardial Infarction in Popular Film
Authors: Kirsten E Shaw, Amy Diedrich, Amy Holbrook, Michelle D Carlson, Kevin M Harris, Retu Saxena
Journal: Circulation (2023)

Introduction: The representation of cardiovascular disease (CVD) in popular media plays a pivotal role in shaping public conceptions about CV health. CVD is the leading cause of death among women and disproportionately affects racial/ethnic minority populations in the United States, yet recent national surveys indicate a significant decline in public awareness. Our study sought to investigate the portrayal of acute myocardial infarction (AMI) in popular film. Hypothesis: Portrayal of AMI in film will predominantly show white men exhibiting symptoms of chest pain. Women, racial/ethnic minority populations, and subtle symptoms of AMI will be underrepresented. Aims: To examine 100 full length feature film scenes depicting AMI and evaluate the representation of gender, race/ethnicity, and symptoms. Methods: The 100 most popular films with scenes depicting AMI were identified using the Internet Movie Database (IMDb). Scenes and AMI symptoms were analyzed by cardiologists/cardiology fellows. Gender and race/ethnicity were acquired via movie plots/scripts or via actor self-identification if the former was unavailable. Results: Of the 100 scenes analyzed, 10% depicted women. The representation of people of color was only 6% in contrast to the 94% of scenes featuring non-Hispanic whites. Of the 10 women portrayed, 1 was non-white. The distribution of gender and race/ethnicity for all scenes is shown in Figure 1. The most prevalent presenting symptom observed in 65% of scenes was chest pain accompanied by loss of consciousness. Conclusions: Popular film depictions of AMI appear to be under representative of women and racial/ethnic minority populations. This may be a contributing factor to the inaccurate public perception that CVD does not affect these populations. Film depictions of AMI, which predominantly portray dramatic symptoms of chest pain and loss of consciousness may also perpetuate false beliefs on typical (or even atypical) symptoms of AMI.
Abstract 12579: Intracoronary Thrombolysis, an Option in Coronary Arteries With Unique Characteristics: A Case Series Report
Authors: Jose Ramon R Orozco Martin, ENRIQUE PONCE DE LEON, Mauricio Kuri Ayache, Cesar Alejandro Rodriguez Salinas, Victor Javier Cesena, Roberto Garcia Corral, Fernando Mejia, Allan Mendez Rodriguez, Jesus ivan Morales Escajeda
Journal: Circulation (2023)

Cases Description: Case 1: A 47-year-old male with inferior ST-segment Elevation Myocardial Infarction (STEMI). Percutaneous Coronary Intervention (PCI), showed an ectasic Right Coronary Artery (RCA) with an occlusive thrombus in mid-distal segment, TIMI 0. Thromboaspiration was not successful, proceeding to use intracoronary (IC) Alteplase 15mg. 72 hours later, PCI showed a RCA without stenosis, TIMI 2. Intravascular Ultrasound (IVUS) was used, showing no plaques or dissection. Discharged with Rivaroxaban 20mg QD and Acetilsalicylic acid (ASA) 100mg QD. Case 2: A 38-year-old male, with previous PCI and 1 stent in Anterior Descending Artery (ADA); arrives with STEMI. PCI showed a ADA non-occlusive intrastent thrombus, TIMI 2. IC Alteplase 15mg was used. After 72 hours, PCI identified the ADA with TIMI 3 flow. IVUS and Optical Coherence Tomography (OCT) showed a mild intrastent thrombus and proximal infraexpansion of previous stent. Proximal and medial segments were dilated, and 1 stent was placed distal. IVUS showed adequate expansion. Discharged with Apixaban 5mg BID and Clopidogrel 75mg QD. Case 3: A 64-year-old male, with inferior STEMI. PCI shows an ectasic ADA with a proximal and medial segment thrombus, TIMI 2. Tromboaspiration and posterior IC Alteplase 15mg were used, with TIMI 3 result. PCI 24 hours later, shows the ADA with TIMI 3 flow. IVUS identifies that no angioplasty was needed. Discharged with Ticagrelor 90mg BID and ASA QD. Discussion: IC thrombolysis is a useful method in primary PCI, where there is no favorable anatomy or massive IC thrombus. These cases show the utility of using IC imaging to evaluate the anatomy and thrombotic content of angiographic lesions. There is no consensus in the chronic anticoagulation/antithrombotic management after IC thrombolysis.
Targeting FLT3-TAZ signaling to suppress drug resistance in blast phase chronic myeloid leukemia
Authors: Ji Eun Shin, Soo-Hyun Kim, Mingyu Kong, Hwa-Ryeon Kim, Sungmin Yoon, Kyung-Mi Kee, Jung Ah Kim, Dong Hyeon Kim, So Yeon Park, Jae Hyung Park, Hongtae Kim, Kyoung Tai No, Han-Woong Lee, Heon Yung Gee, Seunghee Hong, Kun-Liang Guan, Jae-Seok Roe, Hyunbeom Lee, Dong-Wook Kim, Hyun Woo Park
Journal: Molecular Cancer (2023)

Abstract Background Although the development of BCR::ABL1 tyrosine kinase inhibitors (TKIs) rendered chronic myeloid leukemia (CML) a manageable condition, acquisition of drug resistance during blast phase (BP) progression remains a critical challenge. Here, we reposition FLT3, one of the most frequently mutated drivers of acute myeloid leukemia (AML), as a prognostic marker and therapeutic target of BP-CML. Methods We generated FLT3 expressing BCR::ABL1 TKI-resistant CML cells and enrolled phase-specific CML patient cohort to obtain unpaired and paired serial specimens and verify the role of FLT3 signaling in BP-CML patients. We performed multi-omics approaches in animal and patient studies to demonstrate the clinical feasibility of FLT3 as a viable target of BP-CML by establishing the (1) molecular mechanisms of FLT3-driven drug resistance, (2) diagnostic methods of FLT3 protein expression and localization, (3) association between FLT3 signaling and CML prognosis, and (4) therapeutic strategies to tackle FLT3 + CML patients. Results We reposition the significance of FLT3 in the acquisition of drug resistance in BP-CML, thereby, newly classify a FLT3 + BP-CML subgroup. Mechanistically, FLT3 expression in CML cells activated the FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway, which conferred resistance to a wide range of BCR::ABL1 TKIs that was independent of recurrent BCR::ABL1 mutations. Notably, FLT3 + BP-CML patients had significantly less favorable prognosis than FLT3 − patients. Remarkably, we demonstrate that repurposing FLT3 inhibitors combined with BCR::ABL1 targeted therapies or the single treatment with ponatinib alone can overcome drug resistance and promote BP-CML cell death in patient-derived FLT3 + BCR::ABL1 cells and mouse xenograft models. Conclusion Here, we reposition FLT3 as a critical determinant of CML progression via FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway that promotes TKI resistance and predicts worse prognosis in BP-CML patients. Our findings open novel therapeutic opportunities that exploit the undescribed link between distinct types of malignancies. Graphical Abstract
Abstract 12542: Effectiveness of Icosapent Ethyl on First and Total Cardiovascular Events in the Metabolic Syndrome: REDUCE-IT MetSyn
Authors: Michael Miller, Deepak Bhatt, Eliot A Brinton, Terry A Jacobson, Philippe G Steg, Armando L Pineda, Steven Ketchum, Ralph Doyle, Jean-Claude Tardif, Christie M Ballantyne
Journal: Circulation (2023)

Introduction: The Metabolic Syndrome (MetSyn) is associated with persistently high risk of cardiovascular (CV) events despite statin treatment. Methods: REDUCE-IT was a multinational, double-blind trial that randomized 8179 high CV risk statin-treated patients with controlled low density lipoprotein cholesterol, and elevated triglycerides, to icosapent ethyl (IPE) 4 grams/day or placebo. In the overall trial, IPE reduced the risk of the primary composite endpoint (CV death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization or hospitalization for unstable angina) and the key secondary composite endpoint (CV death, nonfatal myocardial infarction or nonfatal stroke). Here we examine the prespecified patient subgroup with a history of MetSyn, but without diabetes at baseline. Results: Compared with placebo, IPE use in patients with MetSyn at baseline (n=2866) was associated with a 29% relative risk reduction for the primary composite endpoint (hazard ratio [HR], 0.71 [95% CI, 0.59-0.84]; P &lt;0.0001, absolute risk reduction [ARR]=5.9%; number needed to treat [NNT]=17) and 41% reduction in total (first plus subsequent) events (rate ratio [RR], 0.59 [95% CI, 0.48-0.72]; P &lt;0.0001) (Figure 1). The risk for the key secondary composite endpoint was reduced by 20% (P=0.05) with a 27% reduction in fatal/nonfatal MI (P=0.03), 47% reduction in urgent/emergent revascularization (P &lt;0.0001) and 58% reduction in hospitalization for unstable angina (P &lt;0.0001). Non-statistically significant reductions were observed in fatal/nonfatal stroke (27%), cardiac arrest (44%) and sudden cardiac death (34%). Conclusions: In statin-treated patients, the addition of IPE significantly reduced the risk of first and total CV events in REDUCE-IT patients with a history of MetSyn. The large relative and absolute risk reductions observed support IPE as a therapeutic consideration for high CV risk patients with MetSyn.
Homologous recombination deficiency (HRD) testing on cell-free tumor DNA from peritoneal fluid
Authors: Cyril Roussel-Simonin, Felix Blanc-Durand, Roseline Tang, Damien Vasseur, Audrey Le Formal, Laure Chardin, Elisa Yaniz, Sébastien Gouy, Amandine Maulard, Stéphanie Scherier, Claire Sanson, Ludovic Lacroix, Sophie Cotteret, Lea Mauny, François Zaccarini, Etienne Rouleau, Alexandra Leary
Journal: Molecular Cancer (2023)

Knowing the homologous recombination deficiency (HRD) status in advanced epithelial ovarian cancer (EOC) is vital for patient management. HRD is determined by BRCA1/BRCA2 pathogenic variants or genomic instability. However, tumor DNA analysis is inconclusive in 15-19% of cases. Peritoneal fluid, available in > 95% of advanced EOC cases, could serve as an alternative source of cell-free tumor DNA (cftDNA) for HRD testing. Limited data show the feasibility of cancer panel gene testing on ascites cfDNA but no study, to date, has investigated HRD testing.We collected ascites/peritoneal washings from 53 EOC patients (19 from retrospective cohort and 34 from prospective cohort) and performed a Cancer Gene Panel (CGP) using NGS for TP53/HR genes and shallow Whole Genome Sequencing (sWGS) for genomic instability on cfDNA.cfDNA was detectable in 49 out of 53 patients (92.5%), including those with limited peritoneal fluid. Median cfDNA was 3700 ng/ml, with a turnaround time of 21 days. TP53 pathogenic variants were detected in 86% (42/49) of patients, all with HGSOC. BRCA1 and BRCA2 pathogenic variants were found in 14% (7/49) and 10% (5/49) of cases, respectively. Peritoneal cftDNA showed high sensitivity (97%), specificity (83%), and concordance (95%) with tumor-based TP53 variant detection. NGS CGP on cftDNA identified BRCA2 pathogenic variants in one case where tumor-based testing failed. sWGS on cftDNA provided informative results even when tumor-based genomic instability testing failed.Profiling cftDNA from peritoneal fluid is feasible, providing a significant amount of tumor DNA. This fast and reliable approach enables HRD testing, including BRCA1/2 mutations and genomic instability assessment. HRD testing on cfDNA from peritoneal fluid should be offered to all primary laparoscopy patients.
Abstract 13899: Engineered Tissue Graft Electrically Couples With Swine Host Heart
Authors: Bijay Guragain, Yuhua Wei, Hanyu Zhang, Asher Kahn-Krell, Lei Ye, Greg Walcott, Jack Rogers, Jianyi J Zhang
Journal: Circulation (2023)

Introduction: Adult mammalian hearts are unable to replenish myocytes lost in myocardial infarction (MI). Recent therapies that implant myocytes derived from human induced pluripotent stem cells (hiPSC-CMs) have shown structural integration of the graft, improved cardiac function, and reduced scar size. However, to successfully remuscularize the heart, implanted tissue must integrate electrically. Here, we directly image electrical coupling between engineered grafts and the host. Methods: We created anterior LV MI in 3 immunosuppressed pigs using ischemia-reperfusion. Cardiac spheroids engineered from hiPSC-CMs were implanted into the border zone right after the procedure. Spheroids were transfected with a calcium indicator (GCaMP6). One week post implantation, the animal was sacrificed, and 0.6 mm thick slices of myocardium containing spheroids were obtained (Fig. A). The slices were stained with a voltage-sensitive dye (VSD) for optical mapping. GCaMP6 and the VSD have different emission spectra allowing electrical activation of the host tissue and spheroids to be imaged independently. The slices were activated with both global field stimuli and focal stimuli applied distant from the spheroids. Results: During field stimulation, action potentials in the slice and calcium transients (CaT) in the spheroids were simultaneous. However, during focal pacing, there was propagation across the slices and latency between the pacing pulses and spheroid CaTs (Fig. B, C). This indicates spheroid activation arose from electrical coupling with the host myocardium and not from direct stimulation by the pacing pulse. We observed coupling at 12 spheroid sites in 10 slices. At 6 sites, 1:1 coupling could be maintained at pacing rates up to 4 Hz (Fig. D). Conclusions: To our knowledge, this is the first demonstration of swine host myocardium coupling electrically with a human engineered tissue graft. Coupling occurred within 1 week and enabled the host to drive the graft.